With industrial enterprises above designated size in Hunan Province being the research target, the data envelopment (DEA) model has been used for a calculation of the R&D efficiency of 14 cities and prefectures in Hunan Province. And conducted a hot spot analysis on R&D efficiency. Thiel index has been used to clarify the regional disparity and regional contribution changes of Hunan Province and the four major regional economic sectors, followed by an inquiry into the factors affecting R&D efficiency and the spatial distribution of hot spots based on the Tobit regression model. The results show that R&D efficiency in Hunan Province is characterized with such flaws as low overall level, unbalanced development and insufficient utilization of R&D resources, with the current hot spot “Changsha-centered” pattern and the regional boundary of sub-cold spots finally formed. In view of the above results, it is pointed out that the government should improve the R&D efficiency of industrial enterprises above designated size in Hunan Province from the perspective of overall layout, regional cooperation of cities and prefectures, and output transformation of enterprises.